EFFECTS OF SUGARS AND POLYMERS ON CRYSTALLIZATION OF POLY(ETHYLENE GLYCOL) IN FROZEN-SOLUTIONS - PHASE-SEPARATION BETWEEN INCOMPATIBLE POLYMERS

Purpose, This study examined the effect of third components (low-molec ular-weight saccharides and polymers) on the crystallization of poly(e thylene) glycol (PEG) in frozen solutions, focusing on the relationshi p between their crystallization-inhibiting ability and molecular compa tibility. Methods, Effects of sugars and polymers on the crystallizati on of PEG 3000 in frozen solution were monitored by differential scann ing calorimetry (DSC). Pulsed-NMR was employed to monitor the molecula r mobility of water and solutes in the frozen solutions. Miscibility b etween PEG and third components in aqueous solution was estimated from the lowering of cloud point of PEG 20,000. Thermal analysis of frozen solutions containing some non-crystallizing solutes was used to exami ne the possibility of phase separation in frozen solutions. Results, S ome sugars and polymers inhibited the crystallization of PEG and forme d practically stable amorphous phases among ice crystals. The mobility of solute molecules in the amorphous phase increased above the soften ing temperature of maximally concentrated solutions (T-s), whereas tha t of water molecules appeared at a lower temperature. Mono- and disacc harides that are relatively less miscible with PEG in solution inhibit PEG crystallization to a lesser degree. Two T-s regions were observed in frozen solutions containing both polyvinylpyrrolidone (PVP) and de xtran, at much lower concentrations than those causing aqueous two-pha se separation at ambient temperatures, Conclusions, Ice crystallizatio n raises the concentration of solutes in the remaining solution, which can lead to phase separation in the amorphous phase. Molecular compat ibility between components is an important factor determining their pr opensity to phase separate and crystallize.